Department of Health and Human Services
Public Health Service
National Arthritis and Musculoskeletal and Skin Diseases Advisory Council
Minutes of the 74th Meeting
8:30 a.m. to 3:00 p.m.
CALL TO ORDER
The 74th meeting of the National Arthritis and Musculoskeletal and Skin Diseases Advisory Council was held on June 14, 2011, at the National Institutes of Health (NIH) Campus, Building 31, Conference Room 6. The meeting was chaired by Dr. Stephen Katz, Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).
Council members present
Dr. Lynda F. Bonewald
Dr. S. Wright Caughman (via teleconference)
Dr. Leslie J. Crofford
Dr. Harry C. Dietz III
Ms. Karen B. Evans
Dr. David Eyre
Dr. Gary S. Firestein
Dr. Linda Griffith
Dr. Henry M. Kronenberg
Ms. Ann Kunkel
Dr. Ted Mala
Dr. Regis O'Keefe
Dr. Alice Pentland
Mr. Bradley R. Stephenson, J.D.
Dr. Julio L. Vergara
NIAMS Staff in Attendance
Dr. Carl Baker
Ms. Susan Bettendorf
Dr. Michael Bloom
Dr. Amanda Boyce
Mr. Gahan Breithaupt
Dr. Branden Brough
Ms. Justine Buschman
Dr. Robert Carter
Dr. Faye Chen
Mr. Robert Chen
Dr. Ricardo Cibotti
Ms. Barbara Cohn
Ms. Stephanie Craver
Ms. Robin DiLiello
Dr. Jonelle Drugan
Ms. Elizabeth Elliott
Ms. Sharon Fair
Dr. Nancy Garrick
Ms. Gail Hamilton
Ms. Kaitaia Huynh
Dr. Stephen I. Katz
Ms. Shahnaz Khan
Mr. Mark Langer
Dr. Gayle Lester
Dr. Helen Lin
Ms. Anita Linde
Dr. Kan Ma
Dr. Marie Mancini
Dr. Su-Yau Mao
Dr. Kathryn Marron
Dr. Joan McGowan
Ms. Leslie McIntire
Ms. Sherry Meltzer
Dr. Laura K. Moen
Ms. Regina Mong
Ms. Anna Nicholson
Ms. Melinda Nelson
Dr. Glen Nuckolls
Dr. John O'Shea
Dr. James Panagis
Ms. Vivian Pham
Dr. Charles Rafferty
Ms. Kelli Reid
Ms. Trish Reynolds
Dr. Louise Rosenbaum
Dr. Susana Serrate-Sztein
Dr. William Sharrock
Ms. Theresa Smith
Ms. Allisen Stewart
Ms. Robyn Strachan
Dr. Phil Tonkins
Dr. Hung Tseng
Dr. Bernadette Tyree
Dr. Fei Wang
Dr. Xibin Wang
Dr. Chuck Washabaugh
Ms. Sara Wilson
Dr. James Witter
Other Federal Staff
Dr. Rajiv Kumar, Center for Scientific Review, NIH
Ms. Latonya Malone, Office of the Director, NIH
Ms. Lei McCabe, Office of the Director, NIH
Dr. John McGowan, National Institute of Allergy and Infectious Diseases, NIH
Dr. Antonio Scarpa, Center for Scientific Review, NIH
Members of the Public
Mr. Mark Beckwith, Nevus Outreach
Ms. Roberta Biegel, National Osteoporosis Foundation
Dr. Michelle Boling, University of North Florida
Mr. Michael Bykowski, Consolidated Solutions and Innovations
Ms. Karen Chesbrough, Foundation for Physical Therapy
Ms. Kim Holmes, IQ Solutions
Ms. Annie Kennedy, Muscular Dystrophy Association
Ms. Kimberly McGraw, IQ Solutions
Ms. Michelle Rodrigues, SRI International
Mr. Richie Taffet, Ehlers-Danlos National Foundation
Ms. Charlene York, CureCMD
CONSIDERATION OF MINUTES
A motion was made, seconded, and passed to accept with no changes the minutes of the 73nd Council meeting, held on February 1, 2011.
FUTURE COUNCIL MEETING DATES
Future Council meetings are currently planned for the following dates:
September 27, 2011
January 31, 2012
June 5, 2012
September 11, 2012
February 5, 2013
June 4, 2013
September 10, 2013
DIRECTOR'S REPORT AND DISCUSSION
Dr. Katz welcomed Council members, NIAMS and other Federal staff, and members of the public. He thanked those who attended the scientific symposium commemorating the Institute's 25th anniversary on the day before this Council meeting. He invited attendees to review the NIAMS ShortTakes online, which include more details on many of the topics covered in his Director's Report. Dr. Katz noted that his "Director's Column" recognizes the accomplishments of Dr. Paul Plotz, a long-time investigator in the NIAMS Intramural Research Program (IRP) who retired earlier this year after more than 40 years of federal service.
Dr. Katz introduced Dr. Gary Firestein, Professor in the Department of Medicine at the University of California, San Diego School of Medicine, who was attending his first meeting as a member of the Council. Dr. Katz congratulated Council member Dr. S. Wright Caughman, who participated in the meeting via teleconference, on being appointed as Executive Vice President of Health Affairs, CEO of the Woodruff Health Sciences Center, and Chairman of Emory Health Care at Emory University.
Council members Dr. John Klippel (President and CEO of the Arthritis Foundation), Ms. Jean Pickford (Executive Director of the Foundation for Ichthyosis and Related Skin Types), and Dr. H. Lee Sweeney (William Maul Measey Professor and Chair, Department of Physiology, University of Pennsylvania School of Medicine) were unable to attend this Council meeting.
Personnel Changes at the NIH/NIAMS
At the NIH level, Dr. Martha Somerman will assume leadership of the National Institute of Dental and Craniofacial Research (NIDCR) as its new Director, effective August 29, 2011. She has been serving as the Dean of the University of Washington School of Dentistry since 2002. Dr. Somerman comes to the NIH with a background in laboratory science—her research focuses on understanding tooth root development and on the application of that understanding to regenerative medicine (an area of research that the NIAMS shares with the NIDCR). Dr. Somerman's laboratory will be housed in the NIAMS IRP.
With the departure of Dr. Jeremy Berg from the National Institute of General Medical Sciences (NIGMS), the NIH is recruiting a new NIGMS Director. Dr. Amy Patterson, who had been serving as Acting NIH Associate Director for Science Policy since fall 2008, has been appointed to fill the NIH Associate Director for Science Policy position on a permanent basis. The NIH is continuing its search for a Director for the NIH intramural Center for Regenerative Medicine (NIH-CRM)—an announcement regarding this position is expected by the next Council meeting.
At the NIAMS level, the Institute is recruiting for a Clinical Director. Ms. Robin DiLiello, who has served as the NIAMS Deputy Budget Officer for the past three years, has been selected as the Institute's Chief Budget Officer. Ms. Vivian Pham has joined the NIAMS as the new Deputy Budget Officer. Prior to this appointment, Ms. Pham served as a lead budget analyst in the U.S. Food and Drug Administration's (FDA) Office of the Commissioner.
Dr. Katz recognized Council member Dr. Hal Dietz, the Victor A. McKusick Professor of Medicine and Genetics at the Institute of Genetic Medicine at Johns Hopkins University School of Medicine, for his election to the National Academy of Sciences. Former Council member Dr. Cato Laurencin, Vice President for Health Affairs at the University of Connecticut Health Center and Dean of the University of Connecticut School of Medicine, has been elected to the National Academy of Engineering. Also elected to the National Academy of Engineering was current Council member Dr. Linda Griffith of the Department of Biological and Mechanical Engineering in the Biological Process Engineering Center, Massachusetts Institute of Technology.
NIAMS electronic and print resources received seven commendations at last month's NIH Plain Language/Clear Communications Awards ceremony. Dr. Katz congratulated staff from the NIAMS Office of Communications and Public Liaison and the Office of Science Policy and Planning for these accomplishments. He also noted that 10 NIAMS staff members have been selected for special recognition at the annual NIH Director's Award Ceremony, including Dr. Janet Austin, Dr. Carl Baker, Dr. William Sharrock, and the NIAMS members of the NIH Patient- Reported Outcomes Measurement Information System (PROMIS) Working Group.
Update on Budget and Congressional Activities
With regard to fiscal year (FY) 2011, President Obama signed the Department of Defense and Full-Year Continuing Appropriations Act of 2011 on April 15, following a long series of continuing resolutions. This legislation provides full-year funding to the NIH at $30.917 billion, which represents a 1 percent decrease below the FY 2010 level. The amount for NIAMS is $534.348 million, which is a reduction of $4.7 million (0.9 percent) below FY 2010. Dr. Katz reported that in light of the new budget, the Institute has updated its funding plan for the year. Details of the plan, including the latest policies for reductions to research project grants (RPGs), can be found on the NIAMS Web site.
Looking to FY 2012, President Obama released his FY 2012 budget request to Congress on February 14. The amount requested for the NIH is $31.979 billion, which represents an increase of 3.4 percent above the FY 2011 enacted level. The amount for the NIAMS is $547.891 million, representing an increase of $13.5 million or 2.5 percent above FY 2011.
On May 11, the Senate Appropriations Subcommittee on Labor, HHS, Education, and Related Agencies held a hearing on the FY 2012 budget. NIH Director Dr. Francis Collins was the primary witness. At the hearing, there was much discussion about the proposal to establish the National Center for Advancing Translational Sciences (NCATS), as well as questions concerning disease-specific research underway at the NIH.
Highlights of Selected Recent Scientific Advances
- In a large-scale study, Dr. Livia Casciola-Rosen of Johns Hopkins University and colleagues have demonstrated that the use of statins may be associated with a necrotizing myopathy (Arthritis Rheum. 2011 Mar 63(3):713-21. PMID: 21360500).
- Dr. Keith Elkon's team at the University of Washington has found new insights into how defects in dead cell clearance can lead to lupus. The researchers found that autoimmunity in MFG-E8-deficient mice is associated with altered trafficking and enhanced cross-presentation of apoptotic cell antigens (J Clin Invest. 2011 May 2. pii: 43254. doi: 10.1172/JCI43254. [Epub ahead of print] PMID: 21537078).
- Dr. Dietz and colleagues published back-to-back papers in Science. In examining new drug targets for treating Marfan syndrome, the investigators found that noncanonical TGFß signaling contributes to aortic aneurysm progression in Marfan syndrome mice (Science. 2011 Apr 15;332(6027):358-61. PMID: 21493862). Dr. Dietz and colleagues also found that angiotensin II type 2 receptor signaling attenuates aortic aneurysm in mice through ERK antagonism (Science. 2011 Apr 15;332(6027):361-5. PMID: 21493863).
- The Spine Patient Outcomes Research Trial (SPORT) has yielded a tremendous amount of data that can help to predict which patients will benefit from different treatments. Dr. Mitchell Freedman of Thomas Jefferson University and colleagues examined the impact of diabetes on the outcomes of surgical and nonsurgical treatment of SPORT patients. Not having diabetes is beneficial in terms of better outcomes with regard to lower back surgery, particularly for surgery for intervertebral disc herniation (Spine. 2011 Feb 15;36(4):290-307. PMID: 21270715).
- A study by Dr. Michael Kyba of the University of Minnesota and colleagues found that induced pluripotent stem cells derived from healthy adult animals can multiply in tissue culture and can be manipulated to form a sufficient number of muscle progenitor cells for transplantation (Stem Cell Rev. 2011 Apr 2. [Epub ahead of print] PMID: 21461712).
- Studies by Dr. Thomas Carpenter and his colleagues at Yale University have found that even after a single dose, calcitonin offers hope as a therapy for X-linked hypophosphatemia (N Engl J Med. 2011 Apr 28;364(17):1678-80. PMID: 21524226).
NIH/NIAMS Activities and Plans for the Future
As highlighted in the press a few months ago, the Federal Appeals Court lifted the preliminary injunction that was intended to block federal funding of human embryonic stem cell research. The NIH had been allowed to support human embryonic stem cell research for the past several months while the Administration was appealing the injunction. The Court's ruling is important, both for maintaining viable avenues of scientific inquiry, and for—in the words of Dr. Collins—"the hopes of thousands of patients and their families who are relying on NIH-funded scientists to pursue life-saving discoveries and therapies that could come from stem cell research."
With regard to the PROMIS initiative (which is supported by the trans-NIH Common Fund through 2013 and managed administratively by the NIAMS), a good deal of the work currently focuses on testing and validating the PROMIS instruments in clinical trials for various chronic diseases, including pediatric disorders, arthritis, gastrointestinal distress, and routine clinical care of HIV/AIDS patients. Dr. Katz reported that more than 2,600 investigators in 45 countries have registered to use the PROMIS software and noted that PROMIS cuts across almost every dimension of clinical medicine. There have been more than 100 journal publications related to PROMIS since 2004 (33 publications in 2010 alone).
Discussions continue about how to integrate the Clinical and Translational Science Awards (CTSAs) into the new NCATS. Dr. Katz chairs the committee charged with addressing this issue, which affects many in the scientific community. The NCATS mission is evolving—Dr. Katz and his fellow committee members continue their efforts to define what that mission will be.
Dr. Katz emphasized that new investigators play a key role in harnessing emerging scientific opportunities to benefit public health. At the last Council meeting, NIH Deputy Director for Extramural Research, Dr. Sally Rockey, and discussed NIH plans to assess the workforce needs of the biomedical research community. Since then, the NIH has established a working group to gather input on this matter from the extramural community. As part of their recommendations, the group will develop a model for a sustainable and diverse U.S. biomedical research workforce, using expertise from the NIH and external sources. It is hoped that the model will help inform decisions about how to train the optimal number of people for the appropriate types of positions that will advance science and promote health.
As part of the NIH Center for Scientific Review's (CSR) ongoing efforts to enhance the peer review process and evaluate its operations, the NIH has announced the establishment of a new CSR Advisory Council. This new Council replaces the NIH Peer Review Advisory Committee. One recent change in NIH policy that has received considerable discussion recently is the elimination of the A2 resubmission applications. The NIH is following the outcome of this policy closely.
At its annual Extramural Scientific Planning Retreat, NIAMS staff engaged in discussions regarding the role that the Institute plays in advancing research and patient care, and how it can leverage the lessons surrounding that progress into funding the best, most meaningful grant applications in the future. Three Council members participated in the retreat: Drs. David Eyre (Professor of Orthopaedics and Sports Medicine at the University of Washington), Ted Mala (Director of the Southcentral Foundation Traditional Healing Clinic in Anchorage, Alaska), and Alice Pentland (James H. Sterner Professor and Chair of the Department of Dermatology at the University of Rochester School of Medicine and Dentistry). At the retreat, participants discussed funding strategies in times of flat/decreasing budgets. Dr. Katz explained that the Institute usually sets aside a pool of money for selective payment of meritorious, high-priority grant applications that fall outside the NIAMS' payline. Various portfolio analysis tools exist that provide information about research gaps, opportunities, overlap, and impact.
Although basic research projects comprise the bulk of the Institute's research portfolio, the clinical trials that it supports represent a significant investment of money and time. The NIAMS recently revisited its strategy for supporting clinical trials, with the goal of identifying and funding trials that are as timely and informative as possible and will lead to improvements in clinical practice. In addition to the Pilot and Feasibility Clinical Research Grants (R21) funding opportunity announcement, two new types of solicitations are now available: (1) the Clinical Trials Planning Grants (U34); and (2) a UM1 and a U01 for implementation of full-scale clinical trials once the planning process is complete. Both the planning and the implementation announcements utilize cooperative agreements. Dr. Katz reminded the Council that its Working Group for Clinical Trials will advise the NIAMS about whether it should accept the largest and most costly clinical trials (i.e., those with anticipated budgets of $500,000 or more in a single year).
Dr. Katz concluded his Director's Report by emphasizing that communication is a core component of the NIAMS mission and announcing that the NIAMS public Web site has been rated as a top performer among federal Web sites. Except for Medline and Medline Plus, the NIAMS Web site ranks higher than all other NIH sites. Dr. Katz congratulated the NIAMS Web Team and all staff who help keep the site current, accurate, and informative.
To open the discussion session, Dr. Katz asked Dr. Dietz to expand on his papers that were recently published in Science. Dr. Dietz explained that one paper addressed the issue of whether canonical or noncanonical SMAD-independent signaling is the important driving force in aneurysm, skeletal muscle myopathy, and emphysema in the Marfan mouse models. Dr. Dietz's group found that the SMAD cascades were critical for both muscle disease and lung disease. Unexpectedly, non-canonical TGFß signaling was the driving factor for aneurysm progression. The second paper focused on the use of losartan for preventing aneurysm progression and the pathway for this protective effect. It was discovered that losartan only works in patients with an intact angiotensin 2 type II receptor. These findings help inform the pathogenesis of Marfan syndrome.
Council member Dr. Henry Kronenberg, Chief of the Endocrine Unit at Massachusetts General Hospital and Professor of Medicine at Harvard Medical School, expressed surprise that with a 1 percent decrease in the NIAMS budget, the R01 payline decreases from 14 percent to 11 percent. Dr. Katz explained that the R01 payline depends in part on the number of competing grants submitted in a given year and indicated that additional information would be available at the next Council meeting. Dr. Kronenberg noted that the Institute has the option of making cuts in money previously allocated for outlying years in grants and suggested that this could be a potential alternate option to decreasing the payline to 11 percent. Dr. Katz noted that from 1993-2006, a cost management agreement was built into every grant award that anticipates a 3 percent annual increase. In 2006, there were no inflationary increases in the noncompeting pool of grants. Since 2006, the Institute generally has provided 1-2 percent in inflationary annual increases to grants. CSR Director Dr. Antonio Scarpa noted that overall at the NIH level, the number of applications submitted is increasing (due in some part to projects funded by the American Recovery and Reinvestment Act [ARRA]) while Institutes are faced with flat budgets.
Dr. Firestein asked about NIAMS interactions with the NCATS and CTSAs, particularly in terms of clinical trials funding. He commented that there is an extremely high level of anxiety about how the existence of CTSAs and the NCATS will affect the funding decisions for clinical trials. Dr. Katz noted that the success of the CTSAs would involve an improvement in the processing of how clinical trials are done. Dr. Firestein stated that some NIH Institutes have explicitly stated that they will take into account CTSA subsidies when funding decisions are made.
Council member Dr. Regis O'Keefe, Chair of the Department of Orthopaedics and Rehabilitation at the University of Rochester Medical Center, pointed to the success and popularity of the NIAMS Web site, noting that it clearly reflects the excellence of the site itself as well as the prevalence and importance of musculoskeletal diseases in the United States. Approximately 25 percent of the U.S. health care budget is related to musculoskeletal diseases in terms of direct expenditures for patient care; however, the NIAMS receives a much smaller percentage of the federal government's biomedical research dollars. Dr. O'Keefe asked if there were any plans at the Institute level to work with the Agency for Healthcare Research and Quality (AHRQ) in terms of musculoskeletal diseases (and particularly with regard to comparative effectiveness research and health systems research). Dr. Katz explained that these types of interactions will take place through the \ Patient-Centered Outcomes Research Institute (PCORI) which includes 25 members (AHRQ, NIH, and the U.S. Food and Drug Administration [FDA] are the three permanent PCORI members).
ENHANCING PEER REVIEW DURING CHALLENGING TIMES
Dr. Scarpa reviewed major drivers of change affecting the peer review system within the context of a flat budget. The first driver is the NIH budget, which doubled in the five years from 1998-2003, remained flat until 2009, and then experienced a boost in 2009 and 2010 with ARRA funding. Small, if any, increases to the NIH budget are expected in the coming years.
The NIH budget is not the major driver for paylines, however; that driver is the number of applications submitted to the NIH. Since 1996, the number of applications submitted to NIH has more than doubled (from approximately 40,000 in 1996 to an expected 85,000 in 2011). This dramatic increase has caused havoc on the NIH peer review system (e.g., it required doubling the number of reviewers).
Another driver affecting change to the peer review system is the reviewer's load. The number of applications per reviewer was reduced from an average of 12 in 1997 to 6 in 2005. In 2011, the number of applications per reviewer is expected to be 9.
The CSR budget, which is approximately $100 million, is another factor. Dr. Scarpa reported that the total cost of peer review, including travel and small honoraria for 20,000 reviewers, represents 0.4-0.6 percent of the funds requested by the applicants. The CSR has been able to save approximately $37 million per year through various cost-cutting measures, such as using non-refundable airline tickets, using 4,000 fewer reviewers, having 20 percent of reviewers utilize electronic platforms, holding one review meeting per year on the West Coast, etc. Dr. Scarpa also noted that not all applications are increasing. For example, the R01 submission rate has remained somewhat stable at roughly 30,000 per year for the last 6 years. The R21 submission rate has doubled from 5,000 per year to 10,000 per year in the last 6 years.
To enhance the peer review process, particularly in light of a challenging budget, the CSR is spearheading efforts to improve study section alignment, with input from the scientific community, internal integrated review group (IRG) reviews, open houses, and Advisory Councils. Dr. Scarpa noted that approximately 10 percent of the study sections are changed each year to reflect changing science. The CSR also tries to make study sections broader so that different sciences can compete more effectively. Dr. Scarpa presented slides showing positional maps of study sections to show how the CSR can determine whether a study section is too broad or too narrow.
Dr. Scarpa explained that the CSR has successfully shortened the number of days required to review submitted applications, despite the increasing number of applications it receives. The Center is also advancing additional review platforms (e.g., Internet-assisted meetings, video-assisted meetings, and telepresence meetings) to help recruit reviewers and reduce travel time/expenses.
Dr. Scarpa then reviewed the CSR's strategies that have been successful in helping the Center recruit the best reviewers. These strategies include holding one meeting per year on the West Coast, utilizing additional review platforms, developing a national registry of volunteer reviewers, providing tangible rewards for reviewers (e.g., no submission deadlines for chartered members of study sections), and providing flexible time commitments for reviewers (e.g., choice of three times/year for four years or two times/year for six years).
The CSR is making every effort to identify the most promising research earlier. The NIH abolished the A2 application; Dr. Scarpa commented that this policy has worked extremely well in getting the best research funded earlier in the process. This change and others related to enhancing the peer review process have helped reduce the average time from R01 submission to award from 90 weeks to 50 weeks.
Dr. Scarpa described peer review training activities for CSR and NIH peer review staff, study section Chairs, and reviewers. For example, reviewers are provided with a PowerPoint presentation, interactive training sessions, lists of frequently asked questions, and a mock study section video. The CSR is constantly reviewing the changes it is making to enhance the peer review system (e.g., through a 2009 applicant and reviewer survey, a 2010 Advisory Council survey, and a 2011 planned survey on shorter applications).
In the discussion, Dr. Kronenberg suggested that the mock study section video be made available to applicants as an educational tool. Dr. Scarpa indicated that this video is available on the CSR Web site. He added that the Web site includes a wealth of valuable information for both applicants and reviewers.
Dr. O'Keefe asked if the CSR would be examining any other parameters to gauge its effectiveness in enhancing peer review. He noted that the average age of investigators receiving their first award appears to be trending upwards and asked about whether the changes to the peer review system promote attracting younger people to science and funding more new investigators. Dr. Scarpa noted that Dr. Collins has introduced an R01 equivalent for investigators beginning their postdoctoral careers that has been effective in bringing in new investigators. Overall, the NIH has increased the number of new investigators it funds.
NIAMS Division of Musculoskeletal Diseases Director Dr. Joan McGowan congratulated Dr. Scarpa on the CSR's response to the drivers affecting change to the peer review system as well as the Center's ongoing evaluation efforts. In addition to the large number of applicants (roughly 70,000), other CSR constituents include NIH Institute Directors who make decisions on funding as well as the Program Directors who inform them. She noted that Program Directors are having an increasingly difficult time hearing the reviews (often the only way for Program Directors to attend study section meetings is via teleconference). Dr. McGowan emphasized the need for well-tested and effective telecommunications equipment for study section review meetings. Dr. Scarpa noted that the CSR is aware of these issues (it has tested six types of microphones for use in teleconferences), and that in many cases, the success of a teleconference depends on the study section meeting host facility's equipment.
Dr. Pentland noted that many times, reviewers who give an application poor scores do not include information about the weaknesses in the summary statement. Dr. Scarpa acknowledged that this has been a problem in the past, partly due to NIH's stance that peer review should not take the place of mentoring. He explained that Scientific Review Officers are now asked to confirm that the reviews include sufficient information.
Council member Dr. Lynda Bonewald, Lefkowitz Professor in the Department of Oral Biology at the University of Missouri-Kansas City School of Dentistry, asked if study section meetings had to be held in hotels, and whether university settings might provide better telecommunications equipment. Dr. Scarpa commented that study section meetings cannot be held at universities because this could be construed as a real or apparent conflict of interest.
OSTEOARTHRITIS INITIATIVE CONCEPT CLEARANCE
Dr. Gayle Lester, Health Scientist Administrator within the NIAMS Division of Musculoskeletal Diseases, explained that the Osteoarthritis Initiative (OAI) represents a significant investment by the NIAMS, National Institute on Aging (NIA), and other NIH partners. It provides a database of clinical, biochemical, and imaging resources to serve as a resource for the development of biomarkers and new treatment targets for knee osteoarthritis. Currently, the OAI provides baseline and four-year follow up clinical data and images on approximately 4,800 individuals for use by the research community. Funds were pledged in 2009 to cover costs through 2015 and allow completion of the eight years of follow up on the cohort and close out of the study. Due to a 10-year limit on contracts at the NIH, there is a need to reissue the solicitation for new contracts to complete the study.
The goals of the OAI are to create a research resource that will provide state-of-the-science clinical data and images on a large cohort with clinical osteoarthritis or risk factors for osteoarthritis. These images will be used to aid in identification, evaluation, and validation of biomarkers such as: (1) risk factors for disease onset and progression, (2) measurements of disease progression, and (3) possible surrogates for osteoarthritis clinical trial endpoints. Dr. Lester explained that this contract solicitation will provide the needed time and effort for the completion of data collection for the follow up visits of the OAI cohort. It is anticipated that no additional funds, beyond those currently pledged by NIH Institutes and Centers and the pharmaceutical industry through the Foundation for NIH, will be needed for completion.
The Council voted unanimously in favor of the concept.
2011 NIAMS EXTRAMURAL SCIENTIFIC PLANNING RETREAT
Dr. Katz explained that, in addition to the previously mentioned topics, the 2011 NIAMS Extramural Scientific Planning Retreat also included a focus on an evaluation of the Institute's programs. Dr. Susana Serrate-Sztein, Director of the NIAMS Division of Skin and Rheumatic Diseases, described the goals of the retreat as follows: (1) review ongoing and emerging areas of science; (2) identify needs, gaps, and opportunities that would not be pursued otherwise; (3) review funding mechanisms or activities to develop policies to adapt to the current science and funding environment; and (4) introduce new tools and approaches to conduct science portfolio analysis.
The focus on evaluating NIAMS programs allowed an opportunity for attendees to become familiar with some of the emerging new tools and approaches to conducting portfolio analyses. Portfolio analysis tools were tested for the assessment of outcome indicators of supported research, the evaluation of methods for identifying science trends and contributions of funded research, and improving the understanding of ongoing studies and emerging areas of research.
Drs. Sztein and McGowan reviewed retreat topics and highlighted activities in the following areas:
- Common pathways leading to high-impact discoveries
- Skin innate immunity
- Scleroderma research
- Developments in musculoskeletal tissue engineering and regenerative medicine (TE/RM)
- Research developments and trends in integrative physiology and the genetics of bone
- Muscle disease preclinical translational research
Dr. Firestein asked if the goal in milestone-driven projects is to convert those into contracts instead of grants. Dr. McGowan indicated that this is not the case—contracts are generally used by the Institute only for very specific resource development activities. Dr. Katz added that at the NIH, it is much more difficult to use contracts as opposed to grants for funding research than it was a decade ago or more...
Council member Mr. Bradley Stephenson, an attorney and member of the Muscular Dystrophy Association National Task Force on Public Awareness, asked about moving basic research to clinical and translational research. Patients understand that basic science is important, but there is a degree of impatience from the patient perspective in terms of getting new research discoveries tested in humans. Dr. McGowan agreed that this is a dynamic tension and that clinical investigators share this desire. She commended the muscular dystrophy community for being exemplary in terms of its desire to participate in clinical research when it is ready.
POSSIBLE CORRELATES FOR SCIENTIFIC PROGRESS AND SUCCESS
Dr. John J. McGowan, Deputy Director for Science Management at the National Institute of Allergy and Infectious Diseases (NIAID), discussed a number of key forces impacting science. These include funding, an increasing demand for transparency/accountability, changing workforce demographics, technology driven cultural and economic changes, the expanding use of performance metrics, and developing ways to analyze the impact of funding on scientific discovery and improving public health.
Previously, if there was a desire to analyze product development across the federal government, a large number of data sources would need to be mined and analyzed. An integrated system is needed to sort data and make it easy to analyze the science being funded. This need has led to the development of the eScientific Portfolio Assistant (eSPA), an integrated, iterative analysis reporting tool that is immediate, transparent, and accountable. eSPA is an analytic tool that: (1) builds and tracks outputs and outcomes; (2) links data sources to provide real-time quantitative information for managing scientific portfolios; and (3) allows for retrospective and prospective analyses, funding decisions, policy analysis, and strategic planning. The system can generate a daily personalized portfolio update that can be cross-linked to indicators such as publications, grants, contracts, inventions, patents, clinical trials, and drugs/devices.
Dr. J. J. McGowan provided a series of examples to show how eSPA links data to provide real-time, quantitative information for managing a scientific portfolio. eSPA can be used to help make funding decisions for a particular application and monitor performance. He emphasized that eSPA does not, in and of itself, make funding decisions, but provides users with improved information for making potential funding decisions.
Dr. J. J. McGowan presented a series of eSPA analysis case studies to highlight how the system allows for retrospective and prospective analysis for funding and strategic planning. The eSPA analysis case studies were:
- NIH Type 1 diabetes research program output analysis used to support Congressional reporting on program impact.
- NIAID use of select pay.
- Cost and outcomes analysis of NIH-sponsored select agents research to assess the impact of program policy.
- NIH HIV research portfolio content analysis used for prospective strategic planning.
Dr. J. J. McGowan explained that eSPA is an internal computational tool, deployed within the NIH beginning in 2008. There are more than 1,300 NIH eSPA users and the system performs approximately 460,000 operations per day.
In response to a question from Dr. Kronenberg, Dr. J. J. McGowan indicated that eSPA analyzes a great deal of information that is publicly available, although the system also draws from information that is not available to the public. Dr. O'Keefe asked if eSPA would eventually be taken to study sections and asked about how eSPA data would be used to make funding decisions. Dr. J. J. McGowan explained that the system is a tool for helping to make these decisions and allowing users to further examine which metrics appear to be more valuable than others. Dr. Katz commented that eSPA can be used at many different levels (e.g., the Program Director level, the Division level). He also noted that in some cases, it may be possible that eSPA could be used in study sections. Dr. J. J McGowan added that the system also can help inform decisions related to programmatic balance.
Mr. Stephenson pointed out that the outcomes of NIAID grants funded through traditional mechanisms versus those funded through select pay appeared to be very similar. He asked about a hypothetical scenario involving randomly selecting grants to be funded through select pay. Dr. J. J. McGowan indicated that randomness is variable for different percentile ranges with regard to the success of a given grant application. He noted that the large number of high-scoring grant applications reduces the variance in outcomes between grants awarded through traditional funding decision mechanisms and select pay.
NIAMS FUNDING STRATEGIES
Dr. Katz noted that an evening session of the 2011 NIAMS Extramural Scientific Planning Retreat featured funding strategies in times of flat or decreasing budgets. NIAMS staff was asked to consider "what do we need to do that is different from what we are doing now to maintain the vitality of the research community in arthritis and musculoskeletal and skin diseases?"
Dr. Robert Carter, NIAMS Deputy Director, explained that this portion of the meeting was intended to obtain feedback from Council members regarding the various options the Institute has, given the current budget environment at the NIH. He reminded Council members that the majority of the NIAMS extramural budget supports investigator-initiated research, as evaluated by peer review—peer review forms the basis of all Institute funding decisions. In times of tightening budgets, funding those grant applications with the greatest potential significance becomes more critical to sustaining scientific progress. This effort must be coupled with activities related to scanning the scientific landscape to identify needs, gaps, and opportunities.
Previously, on average, 7 percent of the budget that was available for competing RPGs went to select pay (Dr. Katz reminded Council members that select pay refers to supporting research beyond the payline). Criteria for those select pay awards included high priority research, high innovation, and high potential significance. Portfolio diversity was also a factor when determining select pay of a grant, as was the desire to maintain key resources. Program Directors or Council members can recommend applications for select pay funding, with final decisions made by the Institute Director. With tightening paylines, Dr. Carter commented that there is less assurance that the highest impact projects—particularly those that are high risk—will be funded. Final study section scores correlate more with the individual criterion score for approach and less with the scores for significance or innovation. Although the ranking of applications is the foremost criterion used to make funding decisions, as the payline decreases, it is harder to discriminate among the applications with scores at or near the payline.
As part of the new peer review scoring system, percentile points can only be assigned in whole numbers, and thus there is a greater binning effect. The intention was to increase funding flexibility for NIH Institutes and Centers. But it also makes it more difficult to move up the announced percentile score payline due to the budgetary commitment required to fund the larger number of applications at each percentile, and as a consequence, requires increased decision-making by Institute staff.
An analysis by NIAID of their historical data showed a trend towards increased productivity based on percentile bracket, and grants funded through select pay did as well as the best percentile bracket. But NIAMS data, with far fewer grants, showed no such trends.
Dr. Carter asked Council members whether the NIAMS should increase the percentage of the budget for the competing RPG pool that is reserved for select pay. The goal remains: continuing the steady, healthy success rate of investigator-initiated projects. Other NIH Institutes and Centers have approached this question differently, with various outcomes. Some ICs do not announce a payline, some have varying degrees of selectivity based on percentile ranking, and some use a firm payline. Tools are available to help provide objective measures to support these types of decisions (e.g., eSPA, text-based analyses to group applications). Each of these tools has significant caveats, and care must be taken in how the resulting data are interpreted and used. Regardless of what tool(s) is used, Dr. Carter commented that if select pay is being used, judgment has to enter into the process, starting with peer review followed by programmatic judgment. Programmatic judgment should be criteria-based to the fullest extent possible (i.e., having written criteria used to inform recommendations for select pay). There should be a layered process to ensure that there is consistent oversight across the different program areas and that the process is not reliant on the personality of an individual. Clear and open communication to ensure transparency is also needed.
Dr. Katz opened the discussion session by noting that the NIAMS has clearly stated on its Web site that it does utilize select pay, but that applicants cannot request select pay.
Dr. Dietz commented that the argument in favor of select pay appears to be that the Institute can select grants that align with specific priorities or initiatives. He asked for additional information on this issue, and asked if the NIAMS was enthusiastic about the performance of grants funded through select pay with regard to Institute priorities. Both Drs. Katz and Carter agreed that programmatic needs are one consideration, particularly for instances in which there is an application in an area of need.
Council member Dr. Leslie Crofford, Chief of the Division of Rheumatology in the Department of Internal Medicine at the University of Kentucky, asked if the NIAMS utilizes bridge funding and if so, about the differences between bridge funding and select pay. Dr. Katz explained that the purpose of bridge funding is to allow support for an interim period so a revised application can be submitted and is restricted to A0 applications. Bridge funding is less expensive because it does not involve an obligation for a full four years. In some cases, the Institute has used bridge funding. Dr. Crofford noted that the NIAID appears to allocate twice as much money to bridge funding compared with select pay. Dr. Carter indicated that data from NIAID on the outcomes of these applications would be useful.
Dr. Kronenberg asked about criteria other than portfolio balance that serve as drivers for select pay. Dr. Carter explained that other criteria that could be considered include an investigator's other support and whether there is a unique resource that would no longer be available if its operation were no longer funded by the Institute.
Dr. Griffith asked if the issue of extremely discrepant reviewer evaluations is ever considered. Dr. Katz noted that such highly discrepant evaluations are seen more frequently now than they have been in the past, and these situations make the process extremely difficult for Program Directors. Dr. Serrate-Sztein pointed out the importance of identifying the points on which the reviewers had opposing views—decisions regarding select pay are more difficult when reviewers do not agree about the significance of a project.
In response to a question from Mr. Stephenson, Dr. Carter clarified that the question facing Council members is whether the NIAMS should increase the percentage of funds available for select pay. This would increase the number of grants funded by select pay, but it would be neutral in terms of total numbers of grants awarded. Mr. Stephenson indicated that he favors any move that maintains the flexibility of the Council in its second-level peer review duties and the flexibility of the NIAMS and its Director.
Dr. O'Keefe raised the issue of transparency, noting that clarifying these issues and informing the community about as many of them as possible will be critical, particularly if the amount of money for select pay is increased. Dr. Katz agreed, adding that select pay does boil down to a matter of judgment, and at times it can be difficult to explain how a certain judgment was made. Dr. Pentland commented that increasing the select pay funding could help ensure that certain scientific enterprises in areas of interest to the Institute are maintained.
In response to a question from Council member Dr. Julio Vergara, Distinguished Professor in the Department of Physiology at the University of California, Los Angeles School of Medicine, Dr. Katz explained that the NIAMS could allocate up to ten percent of its total competing pool for select pay, up from the recent average of seven percent. He also indicated that percentiling is done by the CSR and clarified that a percentile is determined by virtue of the last two or three rounds of the study section's scores.
BOARD OF SCIENTIFIC COUNSELORS (BSC) REPORT
This report was given during closed session.
CONSIDERATION OF APPLICATIONS
The Council reviewed a total of 873 applications in closed session requesting $1,136,075,563 in total costs and recommended 873 for $1,136,075,563 in total costs.
PORTFOLIO ANALYSIS – GENETICS OF RHEUMATOID ARTHRITISThis portion of the meeting occurred during closed session.
The 74th National Arthritis and Musculoskeletal and Skin Diseases Advisory Council Meeting was adjourned at 3:00p.m. Proceedings of the public portion of this meeting are recorded in this summary.
I hereby certify that, to the best of my knowledge, the foregoing summary and attachments are accurate and complete.
Laura K. Moen, Ph.D.
Stephen I. Katz, M.D., Ph.D.